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Infection and Immunity, July 2007, p. 3455-3461, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00332-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Recombinant Group B Streptococcus Beta C Protein and a Variant with the Deletion of Its Immunoglobulin A-Binding Site Are Protective Mouse Maternal Vaccines and Effective Carriers in Conjugate Vaccines

Hsiao-Hui Yang, Lawrence C. Madoff, Hilde-Kari Guttormsen, Yong-Dong Liu, and Lawrence C. Paoletti^*

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Received 2 March 2007/ Returned for modification 16 April 2007/ Accepted 22 April 2007

Immunogenic vaccines against group B Streptococcus (GBS) have been created by coupling the GBS capsular polysaccharides (CPS) to carrier proteins. The GBS beta C protein (BCP) serves as an effective carrier while inducing protective immunity against BCP-expressing strains. BCP also binds human immunoglobulin A (IgA), a characteristic that may be undesirable for use in humans. Here, we examined the immunogenicity and protective efficacy of a recombinant GBS BCP (rBCP), an rBCP modified to eliminate its IgA-binding site (rBCP^IgA), and their corresponding GBS serotype III CPS conjugates (III-rBCP and III-rBCP^IgA). Deletion of the IgA-binding site or conjugation to CPS did not alter antigenic BCP epitopes. Recombinant proteins and conjugates elicited specific, high-titered IgG in mice. Antisera to rBCP, rBCP^IgA, III-rBCP, and III-rBCP^IgA opsonized GBS strains A909 (Ia/BCP⁺) and H36B (Ib/BCP⁺) for killing by HL-60 cells; antiserum to III-rBCP and III-rBCP^IgA also opsonized strain M781 (III/BCP^–). Vaccination of female mice with either rBCP or rBCP^IgA protected 40% of their pups challenged with GBS strain A909. Pups born to III-rBCP- or III-rBCP^IgA-vaccinated dams survived at rates of 56% and 66%, respectively. Over 90% of pups born to dams that received the type III CPS conjugates survived challenge with GBS strain M781. In summary, rBCP and rBCP^IgA proteins and the conjugates containing them were immunogenic in mice, inducing both CPS- and protein-specific functional IgG. These results suggest that the rBCP^IgA could be used as a carrier to augment the immunogenicity of the CPS while expanding coverage to GBS strains bearing BCP.

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* Corresponding author. Mailing address: Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115. Phone: (617) 525-7878. Fax: (617) 731-1541. E-mail: lpaoletti{at}rics.bwh.harvard.edu

Published ahead of print on 30 April 2007.

Editor: A. Camilli

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Infection and Immunity, July 2007, p. 3455-3461, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00332-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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